key: cord-0930937-q6m7q0qt authors: Hemmelder, Marc H; Noordzij, Marlies; Vart, Priya; Hilbrands, Luuk B; Jager, Kitty J; Abrahams, Alferso C; Arroyo, David; Battaglia, Yuri; Ekart, Robert; Mallamaci, Francesca; Malloney, Sharon-Rose; Oliveira, Joao; Rydzewski, Andrzej; Sridharan, Sivakumar; Vogt, Liffert; Duivenvoorden, Raphaël; Gansevoort, Ron T; Franssen, Casper F M title: Recovery of dialysis patients with COVID-19: Health outcomes 3 months after diagnosis in ERACODA date: 2022-01-14 journal: Nephrol Dial Transplant DOI: 10.1093/ndt/gfac008 sha: 90625c51243223bd81933b7b6f5a939000d888bc doc_id: 930937 cord_uid: q6m7q0qt BACKGROUND: COVID-19-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients three months after their COVID-19 diagnosis. METHODS: We analyzed data on dialysis patients diagnosed with COVID-19 from February 1(st), 2020-March 31(st), 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residency, and functional- and mental health status (estimated by their treating physician) three months after COVID-19 diagnosis. Complete follow-up data was available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. RESULTS: In 2449 hemodialysis patients (mean ± SD age: 67.5 ± 14.4 years, 62% male) survival probabilities at three months after COVID-19 diagnosis were 90% for non-hospitalized patients (N = 1087), 73% for patients admitted to the hospital but not to an ICU (N = 1165) and 40% for those admitted to an ICU (N = 197). Patient survival hardly decreased between 28 days and three months after COVID-19 diagnosis. At three months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (between 0.8 and 6.3%) or a nursing home (approximately 5%). Higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. CONCLUSIONS: Mortality between 28 days and 3 months after COVID-19 diagnosis was low, and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at three months after diagnosis. The COVID-19 pandemic has a major impact around the world, with dialysis patients being among the patient groups with the highest mortality (1, 2) . If infected with SARS-CoV-2, these patients often develop a serious course of COVID-19 which requires in-hospital care. The European Renal Association COVID-19 Database (ERACODA) Working Group previously reported a 28-day mortality of 25% in dialysis patients during the first pandemic wave (3) . In these patients, age and frailty were the dominant factors independently associated with higher mortality (3) . These findings were confirmed in larger cohorts of patients receiving dialysis (4) (5) (6) . Notwithstanding the high short-term mortality in dialysis patients, most patients were alive at 28 days after the diagnosis of COVID-19, but data on longer-term health outcomes in dialysis patients who survived COVID-19 are virtually absent. It could well be that a relevant proportion of patients experience functional deterioration without recovery or die at a later stage due to the long-term complications of COVID-19 (7) . The aim of this study was to assess the recovery of dialysis patients at three months after COVID-19 diagnosis, in terms of patient survival, residency, and functional-and mental health status. Here, we present the first results on these outcomes, as well as their associations with patient and COVID-19 characteristics. This study is based on data from ERACODA, which contains granular data on adult patients (aged >18 years) with kidney failure who were treated with dialysis or living with a functioning kidney allograft and who developed COVID-19 (8) . The COVID-19 diagnosis was based on a positive result on a real-time polymerase chain reaction (PCR) assay or a rapid antigen test of nasal and/or pharyngeal swab specimens, and/or compatible findings on CT scan or chest X-ray of the lungs. The database uses REDCap software, a secure web application for building and managing hemodialysis, because this was by far the most common dialysis modality in ERACODA and also in general within Europe (10) . We collected detailed information on patient characteristics, including age, sex, ethnicity, frailty, comorbidities, hospitalization, and medication use, and on COVID-19 related characteristics such as symptoms, vital signs, and laboratory test results. Frailty was assessed using the Clinical Frailty Score (11) , which ranges from 1, representing very fit, to 9, representing terminally ill. Comorbidities were recorded at presentation from patient charts and obesity was defined as a Body Mass Index (BMI) >30 kg/m 2 . Information on functional and mental health outcomes was collected once at three months after first presentation with COVID-19. Due to the study design, we had no options to invite individual patients to report on their functional and mental outcome. Since nephrologists generally meet their hemodialysis patients every week and know their patients well, we asked them to report on these outcomes. We composed a standardized questionnaire for this purpose (Appendix 1). If patients had not recovered at three months, we asked which limiting factors were judged to be responsible for not reaching the pre-COVID-19 functional and mental health status and how long they estimated the interval to reach the pre-COVID status. All baseline patient and disease characteristics are presented for the total population, and Table S1 . Overall, 1909 of the 2449 hemodialysis patients (78%) survived the first three months after presentation with COVID-19. Those who survived were younger, had a lower frailty score, less comorbid conditions and less symptoms and signs of COVID-19 at presentation than those who died the first three months (Table S2) . At day 28, the survival probability of hemodialysis patients was 90% in the patients who were not hospitalized, 75% in those who were hospitalized but not admitted to the ICU and 47% in those who were admitted to the ICU. At three months after COVID-19 diagnosis, survival probabilities were 90%, 73% and 40%, respectively. This indicates that there is just a limited effect on survival between 28 days and 3 months after diagnosis. Survival was lower in patients admitted to the ICU when compared with those who were not (P-value Log-rank test <0.0001). Kaplan-Meier curves for the three groups are presented in Figure 1 . Among peritoneal dialysis patients survival probabilities at three months were 86% for patients not hospitalized, 61% for patients hospitalized but not admitted to the ICU, and 67% for those ICU-admitted ( Figure S1 ). The survival probability was lower (P=0.006) in those who were hospitalized but not admitted to the ICU, when compared to those admitted to the ICU. Figure 2 presents the residence of survivors at three months after the COVID-19 diagnosis. Although this variable was unknown for a relatively large proportion of patients (58% of patients who were not admitted, 27% of those hospitalized and 28% of those admitted to the ICU), we observed that in case residence was known, most patients were at home at three months of follow-up (36%, 65% and 61%, respectively). Approximately 5% of the patients (in all 3 groups) lived in a nursing home, whereas the proportion of patients that were in the hospital varied between 0.8% in those that were initially not hospitalized to 6.3% in patients that had been ICUadmitted. Data on functional and mental health status were collected at the time point three months after COVID-19 diagnosis and were available for 854 of the 1014 hemodialysis patients (84%) who were alive at this time point and had follow-up data available ( Figure S2 ). The residence status of these patients is presented in Figure S3 . Characteristics of patients who were excluded from this analysis because of missing values did not differ from those of the included patients, except for active malignancy as comorbidity which was more frequent in patients with missing data and respiration rate which was lower in those with missing data (Table S3) . At three months after COVID-19 diagnosis, according to their nephrologist functional status had recovered to the pre-COVID-19 level in 87% of the patients ( Figure 3A ), whereas this was not the case in 111 patients (13%). The proportion of patients who did not recover was higher in the subgroup admitted to the ICU compared to the other two subgroups. Among those who had not yet recovered, the most important limiting factors were reduced muscle strength (48%), reduced mobility (41%) and tiredness (37%). For 58% of these patients, their nephrologist estimated that they would reach their pre-COVID-19 functional status within one year after diagnosis, while they estimated that this would never happen in 28%. Patients for whom a late (>1 year) or no functional recovery was expected, were older, had a higher frailty score, more often had coronary artery disease as comorbidity and had a lower O 2 saturation (data not shown). There were no statistically significant differences in limiting factors for recovery between patients who were not hospitalized, those hospitalized but not admitted to the ICU, and those admitted to the ICU ( (Table 4 ). Treating nephrologists indicated that 94% of their patients had reached their pre-COVID-19 mental health status at three months after COVID-19 diagnosis ( Figure 3B ). Although mental health tended to be more often impaired in the subgroup of patients admitted to the ICU, this was not statistically different compared to the other 2 subgroups. Among the 51 patients (6%) who had not reached their pre-COVID-19 mental health status, the most commonly mentioned limiting factors were memory loss (35%), depression (31%), and anxiety (18%). For 56% of these patients, their nephrologist expected that the pre-COVID-19 mental status would be reached within the upcoming year, whereas 27% were expected to never fully recover their mental health state. There were no statistically significant differences between the subgroups based on hospital admission (Table 3) . For mental health status, only a higher frailty score (OR: 0.75 per unit; 95%CI: 0.63-0.90) was associated with a lower likelihood of reaching the pre-COVID-19 status ( and mental health (N=6) status precluded a meaningful analysis of the time needed to recover and factors that limited recovery in this group. This study shows that functional and mental health had recovered to the pre-existent level according to their nephrologists in the majority of dialysis patients who were alive at three months after COVID-19 diagnosis. Impaired functional outcome was associated with older age, higher frailty score, and ICU admission, whereas impaired mental outcome was associated only with higher frailty score. Among those who had not fully recovered at three months after COVID-19 diagnosis, 58% of patients were expected to recover functionally and 56% to recover mentally within 1 year. Together, our results show that although the short-term mortality of COVID-19 in hemodialysis patients is high, surviving patients have a good prognosis to recover from COVID-19, both functionally and mentally. We demonstrated that in dialysis patients who were alive at three months after a COVID-19 diagnosis only 13% still had an impaired functional status compared to their pre-COVID-19 status. Not unexpectedly, non-recovery to pre-COVID-19 functional status was more frequent in patients who were admitted to the ICU. The most prevalent limiting factors for functional recovery were reduced muscle strength (48%), reduced mobility (41%) and tiredness (37%). In a French general population cohort, 51% of patients that were admitted for COVID-19 reported in a telephone interview to have at least one persistent symptom, of which 31% had fatigue (14) . In a study from China, patients who survived COVID-19 were interviewed after hospital admission with a series of questionnaires (15) . Fatigue or muscle weakness were reported by as many as 63% of patients six months after COVID-19 onset. A report from Italy demonstrated that 54% of COVID-19 survivors had some form of functional impairment after hospital admission as measured by a short physical performance battery and 2-minute walking test (16) . The frequency of non-recovery of functional health after surviving COVID-19 seems less distinct in our dialysis cohort. The difference in findings may -at least in part-be explained by the fact that dialysis patients already have been adapted to having limited pre-existent functional capacity. (17) . In addition, mortality is high in these patients, which may also lead to the most fit patients to survive. Lastly, differences between these previous studies and our study in the way of assessing functional status may have played a role. Notably, the COVID-19 pandemic has raised levels of anxiety and depression in the general population and in patients with various chronic conditions (18) (19) (20) (21) The results presented in this paper have not been published previously in whole or part, except in abstract format. The ERACODA collaboration is an initiative to study prognosis and risk factors for mortality due to COVID-19 in patients with a kidney transplant or on dialysis that is endorsed by the ERA. The Factors associated with COVID-19-related death using OpenSAFELY CKD is a key risk factor for COVID-19 mortality COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe Outcome of COVID-19 in Adults on Kidney Replacement Therapy: A Regionwide Registry Study Post-COVID" Syndrome: How Deep Is the Damage? ERACODA: the European database collecting clinical information of patients on kidney replacement therapy with COVID-19 The REDCap consortium: Building an international community of software partners The ERA-EDTA Registry Annual Report 2018: a summary A global clinical measure of fitness and frailty in elderly people Multiple Imputation by Fully Conditional Specification for Dealing with Missing Data in a Large Epidemiologic Study Statistical analysis with missing data Four-Month Clinical Status of a Cohort of Patients After Hospitalization for COVID-19 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge Functional Dependence and Mortality in the International Dialysis Outcomes and Practice Patterns Study (DOPPS) Psychological distress and loneliness reported by US adults Immediate psychological responses and associated factors during the initial stage of the 2019 coronavirus disease (COVID-19) epidemic among the general population in China Neuropsychiatric symptoms and quality of life in Spanish Alzheimer's disease patients during COVID-19 lockdown Health-related quality of life in common variable immunodeficiency Italian patients switched to remote assistance during the COVID-19 pandemic The Impact of COVID-19 on the mental health of dialysis patients Patient-reported outcome measures: selection of a valid questionnaire for routine symptom assessment in patients with advanced chronic kidney disease -a four-phase mixed methods study Abbreviations: OR, odds ratio; 95% CI, 95% confidence interval; ICU, intensive care unit. *All variables analyzed crude were included in the multivariable models.